Novel hybrids of thiazolidinedione-1,3,4-oxadiazole derivatives: synthesis, molecular docking, MD simulations, ADMET study,<i>in vitro</i>, and<i>in vivo</i>anti-diabetic assessment

Srinivasa, Mahendra Gowdru; Paithankar, Jagdish Gopal; Birangal, Sumit Rao Saheb; Pai, Aravinda; Pai, Vasudev Baburaya; Deshpande, Shridhar N.; Revanasiddappa, B. C.

doi:10.1039/d2ra07247e

Cited by 13 publications

(4 citation statements)

References 33 publications

(40 reference statements)

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“…However, it should be noted that the in vitro results showed higher α-glucosidase inhibitory activity compared with the in vivo antidiabetic effect. This finding is consistent with the results of other studies where compounds or extracts with high activity in in vitro assays showed lower activity in in vivo studies, possibly owing to differences in their absorption, distribution and metabolism, as well as the complex pathophysiology of DM (Kabach et al, 2003;Oboh et al, 2019;Srinivasa et al, 2023).…”

Section: Discussionsupporting

confidence: 92%

Evaluation of antidiabetic and antioxidant effects of Polygonum cognatum Meisn. and phytochemical analysis of effective extracts

Gözcü,

Uğan,

Özbek

et al. 2023

Biomedical Chromatography

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Polygonum cognatum Meisn. (Polygonaceae) is used both as food and as a folk medicine to treat diabetes. This study aimed to evaluate the effect of the extracts, along with isolated compounds, from P. cognatum aerial parts on diabetes. In vitro studies were conducted using an α‐glucosidase inhibitory assay, while in vivo antidiabetic studies were carried out on streptozotocin‐induced diabetic rats. Effective extracts were subjected to isolation studies, and structures of the compounds were elucidated by spectroscopic methods. The ethyl acetate and n‐butanol extracts had the highest effect in both in vitro and in vivo experiments. They also decreased aspartate transaminase, alanine transaminase and malondialdehyde levels, while increasing glutathione and superoxide dismutase activity in rats. From the active extracts, 11 phenolic compounds were isolated and characterized. Among the isolated compounds, quercetin was found to be the most active according to α‐glucosidase inhibitory activity studies. This study provided scientific evidence for the traditional use of P. cognatum as a folk medicine for treating diabetes. The findings suggest that the ethyl acetate and n‐butanol extracts, as well as quercetin, have the potential for development as antidiabetic agents.

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Section: Discussionsupporting

confidence: 92%

Evaluation of antidiabetic and antioxidant effects of Polygonum cognatum Meisn. and phytochemical analysis of effective extracts

Gözcü,

Uğan,

Özbek

et al. 2023

Biomedical Chromatography

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“…1,3,4‐Oxadiazole clubbed thiazolidinediones 46 a – j were prepared by Srinivasa and coauthors [103] and evaluated for their inhibitory potential against α‐amylase and α‐glucosidase enzymes. Bioassay outcomes revealed that compounds 46 a , 46 b , and 46 j exhibited higher inhibition with IC 50 values ranging from 18.42‐22.60 (α‐amylase) and 17.21–22.25 (α‐glucosidase) than used standard, Acarbose (IC 50 =24.35 and 23.73 μM, respectively).…”

Section: Thiazolidinone Based α‐Amylase Inhibitorsmentioning

confidence: 99%

α‐Amylase Inhibitors Based on Thiazolidinone Skeleton: A Promising Approach in Diabetes Management

Singh,

Sindhu,

Kumar

et al. 2023

ChemistrySelect

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Thiazolidinone scaffold has become a promising scaffold when it comes to therapeutic importance, and researchers are quite interested in it because of its wide range of applications in the different fields of chemistry. The capacity of this nucleus to interact with a variety of biological targets, including the peroxisome proliferator‐activated receptor (PPAR), protein tyrosine phosphatase 1B, aldose reductase, α‐glucosidase, and α‐amylase, has led to the observation of its antidiabetic effect. α‐Amylase (α‐1,4‐glucan‐4‐glucanohydrolase, EC 3.2.1.1) is one of the most important industrial endoamylases capable of hydrolyzing the internal α‐1,4‐glycosidic bonds in polysaccharides with net retention of α‐anomeric configuration in low molecular weight products, such as glucose, maltose, and maltotriose units. The inhibitors of α‐amylase have the ability to lower endogenous activity, which is crucial for the management of agricultural pests as well as the treatment and prevention of human disorders. In the present review, we attempted to compile the most recent studies on thiazolidinone‐based α‐amylase inhibitors, investigate their therapeutic potential in treating diabetes, comprehend the relationships between structure and activity, offer suggestions for future research and translation of these findings into clinical applications. This comprehensive review strives to be a valuable resource for researchers, medicinal chemists, and healthcare professionals involved in developing and applying novel therapeutics for treating metabolic disorders.

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“…(Figure 1). [32][33][34][35][36] Among them, succinimide-thiazolidinedione [37] and thiazolidinedione-1,3,4-oxadiazole showed anti-diabetic effects, [38] thiazolidinedione-oxoindoline [39] and thiazolidinedione-indole hybrids [40] showed anticancer and 1,3,4-thiadiazole-thiazolidinedione hybrids [41] demonstrated significant anti-inflammatory activity.…”

Section: Introductionmentioning

confidence: 99%

Molecular Docking, Synthesis, and Characterization of Furanyl‐Pyrazolyl Acetamide and 2,4‐Thiazolidinyl‐Furan‐3‐Carboxamide Derivatives as Neuroinflammatory Protective Agents

Mudimela,

Giridharan,

Janardhan

2024

Chemistry & Biodiversity

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Microglia are key immune cells in the brain that maintain homeostasis and defend against immune threats. Targeting the dysfunctional microglia is one of the most promising approaches to inhibit neuroinflammation. In the current study, a diverse series of molecular hybrids were designed and screened through molecular docking against two neuroinflammatory targets, namely HMGB1 (2LY4) and HMGB1 Box A (4QR9) proteins. Based on the outcomes of docking scores fifteen compounds; ten furanyl‐pyrazolyl acetamides 11(a‐j), and five 2,4‐thiazolidinyl‐furan‐3‐carboxamide 15(a‐e) derivatives were selected for further synthesis, followed by biological evaluation. The selected compounds, 11(a‐j) and 15(a‐e) were successfully synthesized with moderate to good yields, and structures were confirmed by IR, NMR, and mass spectra. The in‐vitro cytotoxicity was evaluated on microglial cells namely BV‐2, N‐9, HMO6, leukemic HAP1, and human fibroblast cells. Further western‐blot analysis revealed that 11h, 11f, 11c, 11j, 15d, 15c, 15e, and 15b compounds significantly suppressed anti‐inflammatory markers such as TNF‐α, IL‐1, IL‐6, and Bcl‐2. All derivatives were moderate in potency compared to reference doxorubicin and could potentially act as novel anti‐neuroinflammatory agents. This study can act as a beacon for further research in the application of furan‐pyrazole and furan‐2,4‐thiazolidinediones as lead moieties for anti‐neuroinflammatory and related diseases.

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Novel hybrids of thiazolidinedione-1,3,4-oxadiazole derivatives: synthesis, molecular docking, MD simulations, ADMET study,in vitro, andin vivoanti-diabetic assessment

Abstract: As compared to standard medicinal compounds, hybrid molecules that contain multiple biologically active functional groups have greater affinity and efficiency.

Cited by 13 publications

References 33 publications

Evaluation of antidiabetic and antioxidant effects of Polygonum cognatum Meisn. and phytochemical analysis of effective extracts

Evaluation of antidiabetic and antioxidant effects of Polygonum cognatum Meisn. and phytochemical analysis of effective extracts

α‐Amylase Inhibitors Based on Thiazolidinone Skeleton: A Promising Approach in Diabetes Management

Molecular Docking, Synthesis, and Characterization of Furanyl‐Pyrazolyl Acetamide and 2,4‐Thiazolidinyl‐Furan‐3‐Carboxamide Derivatives as Neuroinflammatory Protective Agents

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